Role of CD38 Monoclonal Antibodies and Bispecific Antibodies in Treating Multiple Myeloma

At the 2023 Lymphoma, Leukemia & Myeloma Congress in New York, New York, Ajai Chari, MD, University of California – San Francisco, San Francisco, California, shares his insights on the role of cluster of differentiation 38 (CD38) monoclonal antibodies and bispecific antibodies for the treatment of patients with multiple myeloma (MM).

Transcript:

Hi, my name is Ajai Chari. I'm a professor of clinical medicine and the director of the myeloma program at the University of California, San Francisco. 

My topic here today that I was assigned at the Lymphoma, Leukemia & Myeloma Congress was the role of CD38 monoclonal antibodies as well as bispecifics in myeloma, [and] whether they should be moved up earlier, for example, in maintenance.

I think we know that transplants have been kind of a backbone for transplant-eligible patients, and the question is, does adding a CD38 antibody to [bortezomib, lenalidomide, and dexamethasone] (VRd) improve outcomes---so-called quadruplet? I think the data there seemed to be quite good, CASSIOPEIA and GRIFFIN both showing that the addition of CD38 monoclonal antibodies led to not only improvement in [progression-free survival] (PFS), but also in CASSIOPEIA, overall survival. So, I think that's pretty clear.

Where it's a little bit more murky is, in the post-transplant setting, what is the role of CD38? There, CASSIOPEIA had a double-randomization suggesting that if you didn't get dara[tumomab] upfront, there was clearly a benefit, 70% improvement in the likelihood of progression or death if you got dara[tumomab] after transplant. But, if you got dara[tumomab] upfront, there didn't seem to be a benefit to getting dara[tumomab] afterward.

The problem with that study, though, is the dara[tumomab] was given every 8 weeks and we know pharmacologically, it should be every 4 weeks. The second thing is that the follow-up may not have been long enough. It was only about a 3-year follow-up. Because even the control arm does well, we need to look probably [at] a longer follow-up. The supporting evidence for that is if you look at [measurable residual disease] (MRD) negativity at any point, at 1 year and sustained, it's the highest in patients who got dara[tumomab] throughout.

The other study that would shed some light on this is GRIFFIN, where we have the final analysis that was just published in [The] Lancet, showing that the increasing depth of response doesn't come at induction, [and] doesn't come at the end of transplant. It really comes at the end of that 2-year, suggesting the benefit of maintenance. In fact, we have a paper that will be coming out shortly, showing that the benefit of dara[tumomab], even in MRD-negative patients was almost 80%. I think that's really encouraging data. We'll have to stay tuned.

Now, that doesn't mean, however, I think in the maintenance setting, that everybody should be getting dara[tumomab] forever or isa[tuximab], if that gets approved. Currently, GRIFFIN is for 2 years. I think that's important because when you use a drug to progression, it can have downstream sequelae and worse biological impact. I think we'll need more [overall survival] (OS) data to really cement a role of CD38 and maintenance.

Source: 

Chari A. Maintenance therapy: Should CD38 ab or bispecifics be incorporated? Does MRD inform type or duration maintenance? Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-21, 2023. New York, NY